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Autocrine DNA fragmentation of intra-epithelial lymphocytes (IELs) in mouse small intestine

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Abstract

Intraepithelial lymphocytes (IELs) are present in the intestinal epithelium. Mechanisms of IELs for the protection of villi from foreign antigens and from infections by micro-organisms have not been sufficiently explained. Although more than 70 % of mouse duodenal and jejunal IELs bear γδTCR (γδIELs), the functions of γδIELs are little investigated. We stimulate γδIELs by anti-CD3 monoclonal antibody (mAb) injection. The mAb activates γδIELs to release Granzyme B (GrB) into the spaces surrounding the γδIELs and intestinal villous epithelial cells (IECs). Released GrB induces DNA fragmentation in IECs independently of Perforin (Pfn). IECs immediately repair their fragmented DNA. Activated IELs reduce their cell size, remain for some time in the epithelium after the activation and are ultimately eliminated without leaving the site. We focus our attention on the response of IELs to the released GrB present in the gap surrounding IELs, after activation, in order to examine whether the released GrB has a similar effect on IELs to that observed on IECs in our previous studies. DNA fragmentation is also induced in IELs together with the repair of fragmented DNA thereafter. The time-kinetics of both events were found to be identical to those observed in IECs. DNA fragmentation in IELs is Pfn-independent. Here, we present Pfn-independent “autocrine DNA fragmentation” in IELs and the repair of fragmented DNA in IELs and discuss their biological significance. Autocrine DNA fragmentation has never been reported to date in vivo.

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Authors and Affiliations

  1. Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, 980-8575, Sendai, Japan

    Masaki Ogata, Yuta Ota & Tsunetoshi Itoh

  2. Department of Applied Research, Division of Immunology, Yakult Central Institute for Microbiological Research, Tokyo, Japan

    Masanobu Nanno

  3. Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Japan

    Ryuji Suzuki

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  1. Masaki Ogata
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  2. Yuta Ota
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  3. Masanobu Nanno
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  4. Ryuji Suzuki
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  5. Tsunetoshi Itoh
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Correspondence to Masaki Ogata.

Additional information

This work was in part supported by a Grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (20590181 to M.O. and 21590207 to T.I.) and the Japan Science and Technology Agency (JST).

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Ogata, M., Ota, Y., Nanno, M. et al. Autocrine DNA fragmentation of intra-epithelial lymphocytes (IELs) in mouse small intestine. Cell Tissue Res 361, 799–810 (2015). https://doi.org/10.1007/s00441-015-2151-6

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  • DOI: https://doi.org/10.1007/s00441-015-2151-6

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